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      RIPPLELAB: A Comprehensive Application for the Detection, Analysis and Classification of High Frequency Oscillations in Electroencephalographic Signals

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          Abstract

          High Frequency Oscillations (HFOs) in the brain have been associated with different physiological and pathological processes. In epilepsy, HFOs might reflect a mechanism of epileptic phenomena, serving as a biomarker of epileptogenesis and epileptogenicity. Despite the valuable information provided by HFOs, their correct identification is a challenging task. A comprehensive application, RIPPLELAB, was developed to facilitate the analysis of HFOs. RIPPLELAB provides a wide range of tools for HFOs manual and automatic detection and visual validation; all of them are accessible from an intuitive graphical user interface. Four methods for automated detection—as well as several options for visualization and validation of detected events—were implemented and integrated in the application. Analysis of multiple files and channels is possible, and new options can be added by users. All features and capabilities implemented in RIPPLELAB for automatic detection were tested through the analysis of simulated signals and intracranial EEG recordings from epileptic patients (n = 16; 3,471 analyzed hours). Visual validation was also tested, and detected events were classified into different categories. Unlike other available software packages for EEG analysis, RIPPLELAB uniquely provides the appropriate graphical and algorithmic environment for HFOs detection (visual and automatic) and validation, in such a way that the power of elaborated detection methods are available to a wide range of users (experts and non-experts) through the use of this application. We believe that this open-source tool will facilitate and promote the collaboration between clinical and research centers working on the HFOs field. The tool is available under public license and is accessible through a dedicated web site.

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          Most cited references33

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          High-frequency oscillations in human brain.

          Ripples are 100-200 Hz short-duration oscillatory field potentials that have recently been recorded in rat hippocampus and entorhinal cortex. They reflect fast IPSPs on the soma of pyramidal cells, which occur during synchronous afferent excitation of principal cells and interneuron networks. We now describe two similar types of high-frequency field oscillations recorded from the entorhinal cortex and hippocampus of patients with mesial temporal lobe epilepsy. The first type appears be the human equivalent of normal ripples in the rat. The second, which we have termed fast ripples (FR), are in the frequency range of 250-500 Hz. FR are found in the epileptogenic region and may reflect pathological hypersynchronous population spikes of bursting pyramidal cells.
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            Quantitative analysis of high-frequency oscillations (80-500 Hz) recorded in human epileptic hippocampus and entorhinal cortex.

            High-frequency oscillations (100-200 Hz), termed ripples, have been identified in hippocampal (Hip) and entorhinal cortical (EC) areas of rodents and humans. In contrast, higher-frequency oscillations (250-500 Hz), termed fast ripples (FR), have been described in seizure-generating limbic areas of rodents made epileptic by intrahippocampal injection of kainic acid and observed in humans ipsilateral to areas of seizure initiation. However, quantitative studies supporting the existence of two spectrally distinct oscillatory events have not been carried out in humans nor has the preferential appearance of FR within seizure generating areas received statistical evaluation based on analysis of a large sample of oscillatory events. Interictal oscillations within the bandwidth of 80-500 Hz were detected in Hip and EC areas of patients with mesial temporal lobe epilepsy using wideband EEG recorded during non-rapid eye-movement sleep from chronically implanted depth electrodes. Power spectral analysis showed that oscillations detected from Hip and EC areas were composed of two spectrally distinct groups. The lower-frequency ripple group was defined by a frequency of 96 +/- 14 Hz (median +/- width), while the higher-frequency FR group had a frequency of 262 +/- 59 Hz. FR oscillations were significantly shorter in duration compared with ripple oscillations (P < 0.0001). In regard to the occurrence of FR and ripples in epileptic Hip and EC, the mean ratio of the number of FR to ripples generated in areas ipsilateral to seizure onset was significantly higher compared with the mean ratio of FR to ripple generation from contralateral areas (P = 0.008). Furthermore, sites ipsilateral to seizure onset with hippocampal atrophy had significantly higher ratios compared with sites contralateral to both seizure onset and hippocampal atrophy (P = 0.001). These data provide compelling quantitative and statistical evidence for the existence of two spectrally distinct groups of limbic oscillations that have frequency and duration characteristics similar to those previously described in epileptic rat and human Hip and EC. The strong association between FR and regions of seizure initiation supports the view that FR reflects pathological hypersynchronous events crucially associated with seizure genesis.
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              High-frequency oscillations (HFOs) in clinical epilepsy.

              Epilepsy is one of the most frequent neurological diseases. In focal medically refractory epilepsies, successful surgical treatment largely depends on the identification of epileptogenic zone. High-frequency oscillations (HFOs) between 80 and 500Hz, which can be recorded with EEG, may be novel markers of the epileptogenic zone. This review discusses the clinical importance of HFOs as markers of epileptogenicity and their application in different types of epilepsies. HFOs are clearly linked to the seizure onset zone, and the surgical removal of regions generating them correlates with a seizure free post-surgical outcome. Moreover, HFOs reflect the seizure-generating capability of the underlying tissue, since they are more frequent after the reduction of antiepileptic drugs. They can be successfully used in pediatric epilepsies such as epileptic spasms and help to understand the generation of this specific type of seizures. While mostly recorded on intracranial EEGs, new studies suggest that identification of HFOs on scalp EEG or magnetoencephalography (MEG) is possible as well. Thus not only patients with refractory epilepsies and invasive recordings but all patients might profit from the analysis of HFOs. Despite these promising results, the analysis of HFOs is not a routine clinical procedure; most results are derived from relatively small cohorts of patients and many aspects are not yet fully understood. Thus the review concludes that even if HFOs are promising biomarkers of epileptic tissue, there are still uncertainties about mechanisms of generation, methods of analysis, and clinical applicability. Large multicenter prospective studies are needed prior to widespread clinical application. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                24 June 2016
                2016
                : 11
                : 6
                : e0158276
                Affiliations
                [1 ]Department of Biomedical Engineering, Universidad de los Andes, Bogotá D.C., Colombia
                [2 ]Centre de Recherche de L’Institut du Cerveau et de la Moelle Epinière (CRICM), INSERM UMRS 975—CNRS UPR640, Hôpital de la Pitié-Salpêtrière, Paris, France
                [3 ]Department of Electrical and Electronics Engineering, Universidad de los Andes, Bogotá D.C., Colombia
                [4 ]Department of Electronics Engineering. Pontificia Universidad Javeriana. Bogotá D.C., Colombia
                University Paris 6, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MN MV MLQ. Performed the experiments: MN CAR. Analyzed the data: MN CAR MLQ MV. Contributed reagents/materials/analysis tools: MN MV. Wrote the paper: MN CAR MLQ MV.

                Author information
                http://orcid.org/0000-0002-4903-2156
                Article
                PONE-D-15-53346
                10.1371/journal.pone.0158276
                4920418
                27341033
                00e8c70a-7c10-4347-90ca-45bdd052effe
                © 2016 Navarrete et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 8 December 2015
                : 13 June 2016
                Page count
                Figures: 13, Tables: 2, Pages: 27
                Funding
                Funded by: COLCIENCIAS
                Award ID: 567
                Award Recipient :
                This research was partially supported by COLCIENCIAS (Grant 567), http://www.colciencias.gov.co/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Likewise, there was no additional external funding received for this study.
                Categories
                Research Article
                Engineering and Technology
                Signal Processing
                Signal Filtering
                Research and Analysis Methods
                Bioassays and Physiological Analysis
                Electrophysiological Techniques
                Brain Electrophysiology
                Electroencephalography
                Biology and Life Sciences
                Physiology
                Electrophysiology
                Neurophysiology
                Brain Electrophysiology
                Electroencephalography
                Medicine and Health Sciences
                Physiology
                Electrophysiology
                Neurophysiology
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                Electroencephalography
                Biology and Life Sciences
                Neuroscience
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                Brain Electrophysiology
                Electroencephalography
                Biology and Life Sciences
                Neuroscience
                Brain Mapping
                Electroencephalography
                Medicine and Health Sciences
                Diagnostic Medicine
                Clinical Neurophysiology
                Electroencephalography
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                Imaging Techniques
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                Physical Sciences
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                Research and Analysis Methods
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                Signal Filtering
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                Computer and Information Sciences
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                Physical Sciences
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                Medicine and Health Sciences
                Neurology
                Epilepsy
                Engineering and Technology
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                Custom metadata
                All patient files are available from the EPILEPSIAE database ( http://epilepsy-database.eu/). Software scripts are freely available at https://github.com/BSP-Uniandes/RIPPLELAB.

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